CA2014721C - Concentrated aqueous solution of glutaraldehyde and 1,2-benzisothiazolin-3-one - Google Patents
Concentrated aqueous solution of glutaraldehyde and 1,2-benzisothiazolin-3-one Download PDFInfo
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- CA2014721C CA2014721C CA002014721A CA2014721A CA2014721C CA 2014721 C CA2014721 C CA 2014721C CA 002014721 A CA002014721 A CA 002014721A CA 2014721 A CA2014721 A CA 2014721A CA 2014721 C CA2014721 C CA 2014721C
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- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/50—Treatment of water, waste water, or sewage by addition or application of a germicide or by oligodynamic treatment
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
- A01N35/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aliphatically bound aldehyde or keto groups, or thio analogues thereof; Derivatives thereof, e.g. acetals
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
Abstract
Concentrated aqueous solutions of 1,2-benzi-sothiazolin-3-one are prepared by incorporating a buffering agent such that the pH of the solution is between about 3.0 and 7.0, and further adding a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-3-one is in solution than would be in solution if such glutaraldehyde were not present. Also disclosed is a synergistic biocidal composition comprising glutaraldehyde and 1,2-benzisothiazolin-3-one, as well as an aqueous-based industrial composition comprising such synergistic biocidal composition.
Description
TCT CASE NO. Z/WS 35186 -1- ..a 'w'.~.~.
CONCENTRATED AQUEOUS SOLUTION OF GLUTARALDEHYDE
BIND 1,2-EENZISOTHIA20LIN-3-ONE
Field of the Invention The present invention is directed to a~n aqueous composition comprising 1,2~-benzisothiazolin-3-one in water, which c~mposition further comprises a buffering agent such that the pH of the composition is between about 3.0 and 7.0, and a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-3-one is in solution than would be present in solution if such glutaraldehyde were not gresent. This composition, which exhibits desirable storage stability, may be diluted and employed as a biocidal composition which exhibits synergistic activity.
Background of the Invention Glutarald~hyde and 1,2-benzisothiazolin-3-one are both individually known to exhibit desirable biocidal activity. Thus, Payee et al (U.S. Patent No.
~4,1S8B37b) dlisclases that 1,2-benzisothi~zolin-3-one is known to be a very ~ff~ective biocide, parti~L~larly .. for the proteatian of aqueous media against infection by microorganisms. Similarly Clifford e~ al (U. S.
Patent No. 4,338,071) exemplify the biocidal efficacy of glutaraldehyde alone.
CONCENTRATED AQUEOUS SOLUTION OF GLUTARALDEHYDE
BIND 1,2-EENZISOTHIA20LIN-3-ONE
Field of the Invention The present invention is directed to a~n aqueous composition comprising 1,2~-benzisothiazolin-3-one in water, which c~mposition further comprises a buffering agent such that the pH of the composition is between about 3.0 and 7.0, and a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-3-one is in solution than would be present in solution if such glutaraldehyde were not gresent. This composition, which exhibits desirable storage stability, may be diluted and employed as a biocidal composition which exhibits synergistic activity.
Background of the Invention Glutarald~hyde and 1,2-benzisothiazolin-3-one are both individually known to exhibit desirable biocidal activity. Thus, Payee et al (U.S. Patent No.
~4,1S8B37b) dlisclases that 1,2-benzisothi~zolin-3-one is known to be a very ~ff~ective biocide, parti~L~larly .. for the proteatian of aqueous media against infection by microorganisms. Similarly Clifford e~ al (U. S.
Patent No. 4,338,071) exemplify the biocidal efficacy of glutaraldehyde alone.
3Jhile the blending of glutaraldehyde with other biocides, sueh as 2-methyl-4-iso~thiazolin-3-one and 5-chloro-2-methyl-4-isthiazolin-3-one has been accomplished with desirable results in the past (see, e.g., U.S. Patent No. 4,539,0?1 to Clifford et al), similar results have not been exemplified for blends of glutaraldehyde with 1,2-benziso~thia~olin-3-one. It is believed that this stems in large part from the perceived incompatibility of glutaraldehyde with 1,2-benzisothiazolin-3-one.
Thus, it is well accepted that glutaraldehyde should be formulated into aeidic compositions, as this compound polymerizes rapidly in alkaline environments.
See, e.g., K.-E. Rasmunen et al, "Glutaraldehyde. The Influence of pH, Temperature and Buffering on the Polymerization Rate'°, Histochemistry, '~ol. 38, pp.
19-26 (1979); S. Thomas et al, "Temperature-Induced Changes in the Sporicidal Activity and Chemical Properties of Glutaraldehyde", Applied Microbiology, Vol. 2S, No. 3, pp. 331-335 (Sept., 1974). '6ahile Japanese Patent Publication 63-112532 does disclose weakly alkaline aqueous glutaraldehyde solutions, such result is only achieved at the expense of biocidal activity.
Conversely, due to the low solubility of 1,2-benzisothiazolin-3-one in water under acidic conditions, it has become well accepted that this compound must be formulated under alkaline conditions to produce concentrated squeous solutions. Thus, for example, tl.K. Patents Numbers l,l?7.,253 and 1,330,531 both show aqueous formulatlans o~ 1,2-benzisothia-zolin-3-one which are Stabilized by the addition of an appropriate amine or mixture of amines.
Consequently, it is completely unexpected that a concentrated aqueous solution of 1,2-benziso--thiazolin-3-one and glutaraldehyde could be prepared, much less that such combination, when diluted by adding it to an aqueous-based industrial product, would exhibit synergistic biocidal activity.
I?ESCRIPTION OP THE INVENTION
In one aspect,, this invention is directed to a concentrated aqueous composition compxising 1,2-benzisothiazolin-3-one and water, which composition further comprises a buffering agent such that the pH
of the composition is between about .3.0 and 7.0, and a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-3-one is in solut~.on than would be present in solution if such glutaraldehyde were not present.
In other aspects, this invention is directed to a synergistic biocidal eomposition comprising glutaraldehyde arid 1,2-benzisothiazolin-3-one as well as to an aqueous-based industrial product comprising an effective amount of such a synergistic composition.
The concentrated aqueous composition of this invention comprises four components -- i.e., glutar-aldehyde, 1,2-benzisothiazolin-3-one, water and a buffering agent.
As is employed herein, the term ''buffering agent" refers to any compound and/or combinatioxl of compounds which will ~oaintain the pH of the composi-Lion at between about 3.0 and 7.0, preferably at between about 3.2 and aborut 6.b, most preferably between about 3.Z and about 4.8~ and which will a~ot adversely interfere w3~'h 'the biocidal activity of the composition.
r~
Sueh buffering compositions ,are well known to those skilled in the art, and will typically comprise a partially neutralized blenel of an acid and an appropriate base, althoc~gh substances which contain basic and acidic groups which can combine with added base or acid may also be employed. Tllustrative of such buffering agents include the combination of a weak acid, such as acetic, formic, chloxoacetic or propionic acid or the lake, with an appropriate base 1~~ such as sodium hydroxide, sodium acetate or the ~,ike.
A particularly preferred buffering agent for use in the concentrated composition of this invention comprises acetic acid and sodium acetate. The rela-tive amounts of each component in such buffering agents may be readily calculated by one of ordinary skill in the art from buffer tables such as (hose present in the "CRC Handbook of Chemistry and Physics", CRC press, Inc. pp. ID-1G4 et seq., 66th Rd. (19!35-669.
The concentrated aqueous compositions of this invention may be 3:ormed by mixing the components in any order under agitation. Typically, however, an appropriate amount of 1,2-benzisothiazolin-~-one is added to a solution a~f glutaraldehyde under agitation.
The buffering agent is then added whale the agitation continues. Such agitation may be accomplished t>y any means well known to one of ordinary skill in the: art, including mechanical stirrers, magnetic stirrers, ultrasonic agitation means, and the like. In c:Lrcum-stances where a mare concentrated solution of 1.,2-benzi-3U sothiazolin-3-one is desired, it 3.s preferred that an .
excess of such compound be added to an appropriaxtely buffered aqueous glutaraldehyde solution, end the mixture filtered to remove undissolved 1,2-benzisothia-zolin-~-ane and insoluble impurities.
e.
Preferably the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one employed in the eomposi-tions of this invention may range between about 50:1 and about 5:1, and will more preferably be between about 20:1 and about 10:1, most preferably between about 15:1 and about 13:1. Preferably, the weight ratio of active material ~i.e. glutaraldehyde plus 1,2-benzisothiazolin-3-one) to water will range between about 1.0:1 and.about 1.2:1, although lower or higher ratios may be employed, so long as more 1,2-benzisothiazolin-3-one is in solution than would be in solution if no glutaraldehyde mere present.
The amount of buffering agent which should be employed for any particular concentrated composi tiara maybe readily determined by one of ardinary skill in the art. It should be noted that, although concentrated solutions of glutaraldehyde typically possess a pH between about 3.0 and 7.0, a buffering agent is necessary in the 1,2-benzisothiazolin-3-one/
glutaraldehyde blends to avoid pH drift which would adversely affect the storage stability of such composi-tions, expecially at extreme temperatures.
The concentrated aqueous compositions of this inventl.on axe typically employed as biocidal agents in aqueous-based industrial products by adding them to such products in appropriate amounts such that a biacidally effective mount of active material is present in such industrial products. Illustrative of the industrial products in which such combinations may ~0 be employed are calcium carbonate slurries, kaolin slurries, tape ,joint compounds, and latices. The compositions of such aqueous-based industrial camposi-d ons are well known to those of skill in the art.
'These concentrated compositions exhib it admirable long term stability as well as desirable temperature !.
resistance.
An unexpected benefit which has been recog-nized in conjunction with the invention of the concen-trated solutions described above, is that synergistic biocidal activity is achieved when 1,2-benzisothiazolin-3-one is employed together with g;lutaraldehyde.
Because such synergy is observed even at concentrations of active material well below those of the concentrated liquid compositions described above, it is to be noted that such synergy will be present even in non-concen-trated formulations of glutaraldehyde with 1,2-benzi-sothiazolin-3-one wherein no buffering agent is present. Accordingly, in another aspect, this inven-tion is directed to a synergistic biocidal composition comprised of 1,2-benzisothiazolin-3-one and glutaralde-hyde.
Preferably the weight ratios of glutaralde-hyde to 1,2-benzisothiazalin-3-one employed in such synergistic compositions may range from about i7:1 to ab~ut 12.5:1, more preferably from about 15;1 to about 1~:1. the control exhibited by such combinations is greater than that which would have been expected were mere additive results involved.
such synergistic compositions are employed in synergistic amount s -- i.e., amounts in which less than complete control would be expected for either of the components used alone, or both components if only additive contxol were expected. Such compositions may be usefully employed in the industrial products described above.
Examples 'the following Examples are intended to further illustrate the present invention and are not P ~, intended to limit the scope of the invention in any mannex whatsoever.
Hxam~ple 1 Several solutions of deionized water and a buffering agent iaere prepared possessing pH's of ~.2, 4.8 and 6.8 respectively. Specifically 0.2 ~I acetic acid and 0.2 M sodium a~.etate were utilized. A pH 3.2 solution was attained by adding 12.5 ml of 0.2 M
acetic acid to 100 ml of deionized water. The pH 4.8 solution was prepared by adding 22.5 ml of 0.2 M
acetic acid plus 2?.5 ml of 0.2 M sodium acetate brought to a total volume of 100 ml with deionized water. Finally the pH of 6.g solution was created by adding 4.1 ml of 0.2 M sodium acetate plus 1 drop of 0.2 M acetic acid to 100 ml of deionized water. The solubility of 1,2-benzisothiazolin~3aone ("BIT°'), in the form o~ Proxelc press Paste comprising ?~~ BIT as an industrial grade wet powder (available from Imperial Chemical Industries PLC3, in each solution at 25°C was detertained by adding known quantities of BIT while agitating such solutions, filtering off the undissolved BIT; and any insoluble impurities then weighing the filtrate to determine how much BIT was in solution.
Employing the same buffering agents, solutions with 50X aqueous glut~raldehyde were prepared having pH's of 3.2, 4.8 and 6.8 respectively. A twenty ml solution having a pH of 3.2 ores ~ttairaed with 1.45 ml of acetic acid. the twenty ml solution having a pH of 4.8 contained acetic acid and sodium acetate in a 3:1 ' weight 'ratios and the twenty ml solution having a pH
of 6.8 contained 1.25 g of sodium acetate. The solubility of BIT in each solution was determined as ~5 described above. The results of such tests, presented _g_ in grams of BIT soluble per 100 grams of solvent, are summarized in Table 1 below.
TABLE I
Solubility of BIT (in ~rams%100 gams solvent) SOLiIENT pF~ ~ ~ 2 ~~H 4 . 8 I°p I ~ . 8 Deionized b~later '0.32 0.11 0.04 50~ Aqueous Glutaraldehyde - 3.18 3.38 3.04 The above results indicate that the solubil-ity of 1,2-benzisothiazolin-3-one is inereased consid-erably by the addition of glutaraldehyde under the above conditions.
Example 2 In order to compare the composition of the present invention with that disclosed in IJ.S. Patent No. 6,539,071 (Clifford et al) a stable aqueous composition of isothiazolone, the following experiment was p~rfoxnned. To deionized water were added 0.2 percent cupric nitrate, 9 percent magnesium chloride and 15 percent magnesium nitrate, all in percent by weight. The solubility of I,2~benzisothiazolin-3-one in such solution $aas found to be essentially rail, thereby showing that such prior art method for prov~.d~.ng stable aqueous solutions ~f isothizaolones is ineffective for producing a stable aqueous solution of 1,2-benzisothiazolin-3-one.
Examt~le 3 Several forty gram samples of a calcium carbonate slurry (Gamma-Fil 90, available from the _9_ Georgia Marble Company) which were free of microbial growth, were prepared. These samples were divided into four groups. The first group was dosed with varying amounts of glutaraldehyde (in the form of a 50 percent aqueous solution); the second group was dosed with varying amounts of 1,2-benzisothiazolin-3-one;
the third group was dosed with varying amounts of glutaraldehyde (in the form of a 5'0 percent aqueous solution) and of 1,2-bea~zisothiazolin-3-one (in the form of Proxel~ Press fas°te) in a 14x1 z~atio by weight of glutaraldehyde:BIT; a fourth group was left untreated as a control. These samples were each inoculated three times on a weekly basis with an inoculum which contained the following microorganisms:
Acinetobacter calcoaceticus, _Pseudomonas sera inosa, EnterobaGter cloacae and Escherichia _coli. The minimum inhibitory concentration (MIC) values were determined for preservative levels effective in reducing the contaminating microorganisms to less than ten colany forming units/ml fox the first three groups. The number of colony forming units~ml in the control group was also determined. The results of sueh evaluation are summarized in TABLE II below.
TABLE II
htIC values (in parts per million of Active Ingredient) Calcium Carbonate Slurry Week 1 6Je~k 2 Week 3 Glutaraldehyde 250 S00 500 BIT 255 >5?0 380 BIT -~ Glutaraldehyde 265 265 265 (1: I4) Control 3.3 X 106 9.2 X 106 1.8 X 10?
~.~r~~ ~#1.
example 4 A sample of kaolin slurry with significant microbial spoilage was dosed with a range of concen-trations of 1,2-benzisothiazolin-3-one, glutaraldehyde, and 1,2-benzisothiazolin-3-one plus glu~taraldehyde .
(1:14 t~reight ratio). A sample saes included, anti-rnicrobial free, for control purposes with determina-tions of tlae colony forming unitsJml. MIC values (in parts per million of Active Ingredient) to reduce microbial contamination to less than ten colony forming units/ml were determined by the absence of detectable growth by dilution plate counts. The results of such testing are summarized in fable III.
TABLF III
bSlC - --Values (PPm): Kaolin Slum Time (Days) I
Glutaraldehyde 250 I50 200 250 BIT 178 >178 >I78 133 BIT + Clutaraldehyde 214 107 260 160 (1:14) Control 3.2 X 107 2.~ X 10~ 5.~ X 107 1.0 X 10~
The results for ~~camples 3 and 4 were quantified ~rith respect to the syzaergy sh~wn through the application of an equation descx3.bed in Bera~nbaum, M.C. "A method for Testing for Synergy with Any Number of Agents" The .lournal of Infectiaus Diseases, Vol 137, No. 2 pp 122-130 (February, 1978). The relevant equation is as follows:
Ac + Bc = Z
'tee ~Jherein:
Ac ~ First antimicrobial active ingredient, effective level in the combination.
Ae ~ First antimicrobial active ingredient, effective independent activity level.
Ee ~ Second antimicrobial agent ingredient, effective level in the combination.
Be ~ Second antimicrobial active ingredient, effective independent activity level.
If Z is less than 1, synergy is present. If Z equals 1, additive interaction is present. Tf Z is greater than l, an antagonistic interaction is present.
The results of such quantification are presented in TABLE IV.
1.5 TABLE IV
Svnert~v Equation Values Substrate Weeks Calcium Carbonate Slurry 1.06 0.5~* 0.55 (Example 3) Days 1 2 g 7 80 Kaolin Slur~~r 0.88 0.74* 0.81* 0.68 (Example 4) *EIT values u~illzed as noted in TABLES II and I:LI
even though actual MIC's are higher, where a greater than symbol (>) is present.
~'he calcium carbonate slurry example shows that while glutaraldehyde undergoes a xeduction in antimicrobial activity during the second and thixd challenges with microbial insults the combinatian '/.
maintains its antimicrobial potency ~ra.th resulting synergy. While the results for creek 1 indicate that some slight antagonism may be observed, it is believed that this result as aaithin experimental error and S biological variability such that no actual antagonism is in fact present.
The kaolin slurry examp7.e indicates consis-tent synergistic interactions, between BIT and glutar-aldehyde.
1Q Therefore, the above results for Examples 3 and 4 illustrate the unexpected synergistic biocidal activity exhibited by the combination of 1,2-benziso-thiazolin-3-one and glutaraldehyde in agueous-based industrial compositions.
Thus, it is well accepted that glutaraldehyde should be formulated into aeidic compositions, as this compound polymerizes rapidly in alkaline environments.
See, e.g., K.-E. Rasmunen et al, "Glutaraldehyde. The Influence of pH, Temperature and Buffering on the Polymerization Rate'°, Histochemistry, '~ol. 38, pp.
19-26 (1979); S. Thomas et al, "Temperature-Induced Changes in the Sporicidal Activity and Chemical Properties of Glutaraldehyde", Applied Microbiology, Vol. 2S, No. 3, pp. 331-335 (Sept., 1974). '6ahile Japanese Patent Publication 63-112532 does disclose weakly alkaline aqueous glutaraldehyde solutions, such result is only achieved at the expense of biocidal activity.
Conversely, due to the low solubility of 1,2-benzisothiazolin-3-one in water under acidic conditions, it has become well accepted that this compound must be formulated under alkaline conditions to produce concentrated squeous solutions. Thus, for example, tl.K. Patents Numbers l,l?7.,253 and 1,330,531 both show aqueous formulatlans o~ 1,2-benzisothia-zolin-3-one which are Stabilized by the addition of an appropriate amine or mixture of amines.
Consequently, it is completely unexpected that a concentrated aqueous solution of 1,2-benziso--thiazolin-3-one and glutaraldehyde could be prepared, much less that such combination, when diluted by adding it to an aqueous-based industrial product, would exhibit synergistic biocidal activity.
I?ESCRIPTION OP THE INVENTION
In one aspect,, this invention is directed to a concentrated aqueous composition compxising 1,2-benzisothiazolin-3-one and water, which composition further comprises a buffering agent such that the pH
of the composition is between about .3.0 and 7.0, and a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-3-one is in solut~.on than would be present in solution if such glutaraldehyde were not present.
In other aspects, this invention is directed to a synergistic biocidal eomposition comprising glutaraldehyde arid 1,2-benzisothiazolin-3-one as well as to an aqueous-based industrial product comprising an effective amount of such a synergistic composition.
The concentrated aqueous composition of this invention comprises four components -- i.e., glutar-aldehyde, 1,2-benzisothiazolin-3-one, water and a buffering agent.
As is employed herein, the term ''buffering agent" refers to any compound and/or combinatioxl of compounds which will ~oaintain the pH of the composi-Lion at between about 3.0 and 7.0, preferably at between about 3.2 and aborut 6.b, most preferably between about 3.Z and about 4.8~ and which will a~ot adversely interfere w3~'h 'the biocidal activity of the composition.
r~
Sueh buffering compositions ,are well known to those skilled in the art, and will typically comprise a partially neutralized blenel of an acid and an appropriate base, althoc~gh substances which contain basic and acidic groups which can combine with added base or acid may also be employed. Tllustrative of such buffering agents include the combination of a weak acid, such as acetic, formic, chloxoacetic or propionic acid or the lake, with an appropriate base 1~~ such as sodium hydroxide, sodium acetate or the ~,ike.
A particularly preferred buffering agent for use in the concentrated composition of this invention comprises acetic acid and sodium acetate. The rela-tive amounts of each component in such buffering agents may be readily calculated by one of ordinary skill in the art from buffer tables such as (hose present in the "CRC Handbook of Chemistry and Physics", CRC press, Inc. pp. ID-1G4 et seq., 66th Rd. (19!35-669.
The concentrated aqueous compositions of this invention may be 3:ormed by mixing the components in any order under agitation. Typically, however, an appropriate amount of 1,2-benzisothiazolin-~-one is added to a solution a~f glutaraldehyde under agitation.
The buffering agent is then added whale the agitation continues. Such agitation may be accomplished t>y any means well known to one of ordinary skill in the: art, including mechanical stirrers, magnetic stirrers, ultrasonic agitation means, and the like. In c:Lrcum-stances where a mare concentrated solution of 1.,2-benzi-3U sothiazolin-3-one is desired, it 3.s preferred that an .
excess of such compound be added to an appropriaxtely buffered aqueous glutaraldehyde solution, end the mixture filtered to remove undissolved 1,2-benzisothia-zolin-~-ane and insoluble impurities.
e.
Preferably the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one employed in the eomposi-tions of this invention may range between about 50:1 and about 5:1, and will more preferably be between about 20:1 and about 10:1, most preferably between about 15:1 and about 13:1. Preferably, the weight ratio of active material ~i.e. glutaraldehyde plus 1,2-benzisothiazolin-3-one) to water will range between about 1.0:1 and.about 1.2:1, although lower or higher ratios may be employed, so long as more 1,2-benzisothiazolin-3-one is in solution than would be in solution if no glutaraldehyde mere present.
The amount of buffering agent which should be employed for any particular concentrated composi tiara maybe readily determined by one of ardinary skill in the art. It should be noted that, although concentrated solutions of glutaraldehyde typically possess a pH between about 3.0 and 7.0, a buffering agent is necessary in the 1,2-benzisothiazolin-3-one/
glutaraldehyde blends to avoid pH drift which would adversely affect the storage stability of such composi-tions, expecially at extreme temperatures.
The concentrated aqueous compositions of this inventl.on axe typically employed as biocidal agents in aqueous-based industrial products by adding them to such products in appropriate amounts such that a biacidally effective mount of active material is present in such industrial products. Illustrative of the industrial products in which such combinations may ~0 be employed are calcium carbonate slurries, kaolin slurries, tape ,joint compounds, and latices. The compositions of such aqueous-based industrial camposi-d ons are well known to those of skill in the art.
'These concentrated compositions exhib it admirable long term stability as well as desirable temperature !.
resistance.
An unexpected benefit which has been recog-nized in conjunction with the invention of the concen-trated solutions described above, is that synergistic biocidal activity is achieved when 1,2-benzisothiazolin-3-one is employed together with g;lutaraldehyde.
Because such synergy is observed even at concentrations of active material well below those of the concentrated liquid compositions described above, it is to be noted that such synergy will be present even in non-concen-trated formulations of glutaraldehyde with 1,2-benzi-sothiazolin-3-one wherein no buffering agent is present. Accordingly, in another aspect, this inven-tion is directed to a synergistic biocidal composition comprised of 1,2-benzisothiazolin-3-one and glutaralde-hyde.
Preferably the weight ratios of glutaralde-hyde to 1,2-benzisothiazalin-3-one employed in such synergistic compositions may range from about i7:1 to ab~ut 12.5:1, more preferably from about 15;1 to about 1~:1. the control exhibited by such combinations is greater than that which would have been expected were mere additive results involved.
such synergistic compositions are employed in synergistic amount s -- i.e., amounts in which less than complete control would be expected for either of the components used alone, or both components if only additive contxol were expected. Such compositions may be usefully employed in the industrial products described above.
Examples 'the following Examples are intended to further illustrate the present invention and are not P ~, intended to limit the scope of the invention in any mannex whatsoever.
Hxam~ple 1 Several solutions of deionized water and a buffering agent iaere prepared possessing pH's of ~.2, 4.8 and 6.8 respectively. Specifically 0.2 ~I acetic acid and 0.2 M sodium a~.etate were utilized. A pH 3.2 solution was attained by adding 12.5 ml of 0.2 M
acetic acid to 100 ml of deionized water. The pH 4.8 solution was prepared by adding 22.5 ml of 0.2 M
acetic acid plus 2?.5 ml of 0.2 M sodium acetate brought to a total volume of 100 ml with deionized water. Finally the pH of 6.g solution was created by adding 4.1 ml of 0.2 M sodium acetate plus 1 drop of 0.2 M acetic acid to 100 ml of deionized water. The solubility of 1,2-benzisothiazolin~3aone ("BIT°'), in the form o~ Proxelc press Paste comprising ?~~ BIT as an industrial grade wet powder (available from Imperial Chemical Industries PLC3, in each solution at 25°C was detertained by adding known quantities of BIT while agitating such solutions, filtering off the undissolved BIT; and any insoluble impurities then weighing the filtrate to determine how much BIT was in solution.
Employing the same buffering agents, solutions with 50X aqueous glut~raldehyde were prepared having pH's of 3.2, 4.8 and 6.8 respectively. A twenty ml solution having a pH of 3.2 ores ~ttairaed with 1.45 ml of acetic acid. the twenty ml solution having a pH of 4.8 contained acetic acid and sodium acetate in a 3:1 ' weight 'ratios and the twenty ml solution having a pH
of 6.8 contained 1.25 g of sodium acetate. The solubility of BIT in each solution was determined as ~5 described above. The results of such tests, presented _g_ in grams of BIT soluble per 100 grams of solvent, are summarized in Table 1 below.
TABLE I
Solubility of BIT (in ~rams%100 gams solvent) SOLiIENT pF~ ~ ~ 2 ~~H 4 . 8 I°p I ~ . 8 Deionized b~later '0.32 0.11 0.04 50~ Aqueous Glutaraldehyde - 3.18 3.38 3.04 The above results indicate that the solubil-ity of 1,2-benzisothiazolin-3-one is inereased consid-erably by the addition of glutaraldehyde under the above conditions.
Example 2 In order to compare the composition of the present invention with that disclosed in IJ.S. Patent No. 6,539,071 (Clifford et al) a stable aqueous composition of isothiazolone, the following experiment was p~rfoxnned. To deionized water were added 0.2 percent cupric nitrate, 9 percent magnesium chloride and 15 percent magnesium nitrate, all in percent by weight. The solubility of I,2~benzisothiazolin-3-one in such solution $aas found to be essentially rail, thereby showing that such prior art method for prov~.d~.ng stable aqueous solutions ~f isothizaolones is ineffective for producing a stable aqueous solution of 1,2-benzisothiazolin-3-one.
Examt~le 3 Several forty gram samples of a calcium carbonate slurry (Gamma-Fil 90, available from the _9_ Georgia Marble Company) which were free of microbial growth, were prepared. These samples were divided into four groups. The first group was dosed with varying amounts of glutaraldehyde (in the form of a 50 percent aqueous solution); the second group was dosed with varying amounts of 1,2-benzisothiazolin-3-one;
the third group was dosed with varying amounts of glutaraldehyde (in the form of a 5'0 percent aqueous solution) and of 1,2-bea~zisothiazolin-3-one (in the form of Proxel~ Press fas°te) in a 14x1 z~atio by weight of glutaraldehyde:BIT; a fourth group was left untreated as a control. These samples were each inoculated three times on a weekly basis with an inoculum which contained the following microorganisms:
Acinetobacter calcoaceticus, _Pseudomonas sera inosa, EnterobaGter cloacae and Escherichia _coli. The minimum inhibitory concentration (MIC) values were determined for preservative levels effective in reducing the contaminating microorganisms to less than ten colany forming units/ml fox the first three groups. The number of colony forming units~ml in the control group was also determined. The results of sueh evaluation are summarized in TABLE II below.
TABLE II
htIC values (in parts per million of Active Ingredient) Calcium Carbonate Slurry Week 1 6Je~k 2 Week 3 Glutaraldehyde 250 S00 500 BIT 255 >5?0 380 BIT -~ Glutaraldehyde 265 265 265 (1: I4) Control 3.3 X 106 9.2 X 106 1.8 X 10?
~.~r~~ ~#1.
example 4 A sample of kaolin slurry with significant microbial spoilage was dosed with a range of concen-trations of 1,2-benzisothiazolin-3-one, glutaraldehyde, and 1,2-benzisothiazolin-3-one plus glu~taraldehyde .
(1:14 t~reight ratio). A sample saes included, anti-rnicrobial free, for control purposes with determina-tions of tlae colony forming unitsJml. MIC values (in parts per million of Active Ingredient) to reduce microbial contamination to less than ten colony forming units/ml were determined by the absence of detectable growth by dilution plate counts. The results of such testing are summarized in fable III.
TABLF III
bSlC - --Values (PPm): Kaolin Slum Time (Days) I
Glutaraldehyde 250 I50 200 250 BIT 178 >178 >I78 133 BIT + Clutaraldehyde 214 107 260 160 (1:14) Control 3.2 X 107 2.~ X 10~ 5.~ X 107 1.0 X 10~
The results for ~~camples 3 and 4 were quantified ~rith respect to the syzaergy sh~wn through the application of an equation descx3.bed in Bera~nbaum, M.C. "A method for Testing for Synergy with Any Number of Agents" The .lournal of Infectiaus Diseases, Vol 137, No. 2 pp 122-130 (February, 1978). The relevant equation is as follows:
Ac + Bc = Z
'tee ~Jherein:
Ac ~ First antimicrobial active ingredient, effective level in the combination.
Ae ~ First antimicrobial active ingredient, effective independent activity level.
Ee ~ Second antimicrobial agent ingredient, effective level in the combination.
Be ~ Second antimicrobial active ingredient, effective independent activity level.
If Z is less than 1, synergy is present. If Z equals 1, additive interaction is present. Tf Z is greater than l, an antagonistic interaction is present.
The results of such quantification are presented in TABLE IV.
1.5 TABLE IV
Svnert~v Equation Values Substrate Weeks Calcium Carbonate Slurry 1.06 0.5~* 0.55 (Example 3) Days 1 2 g 7 80 Kaolin Slur~~r 0.88 0.74* 0.81* 0.68 (Example 4) *EIT values u~illzed as noted in TABLES II and I:LI
even though actual MIC's are higher, where a greater than symbol (>) is present.
~'he calcium carbonate slurry example shows that while glutaraldehyde undergoes a xeduction in antimicrobial activity during the second and thixd challenges with microbial insults the combinatian '/.
maintains its antimicrobial potency ~ra.th resulting synergy. While the results for creek 1 indicate that some slight antagonism may be observed, it is believed that this result as aaithin experimental error and S biological variability such that no actual antagonism is in fact present.
The kaolin slurry examp7.e indicates consis-tent synergistic interactions, between BIT and glutar-aldehyde.
1Q Therefore, the above results for Examples 3 and 4 illustrate the unexpected synergistic biocidal activity exhibited by the combination of 1,2-benziso-thiazolin-3-one and glutaraldehyde in agueous-based industrial compositions.
Claims (14)
1. A composition comprising 1,2-benziso-thiazolin-8-one and water, which composition further comprises a buffering agent such that the pH of the composition is between about 3.0 and 7.0, and a sufficient amount of glutaraldehyde such that a greater amount of such 1,2-benzisothiazolin-8-one is in solution than would be present in solution if such glutaraldehyde were not present.
2. A composition in accordance with claim 1 wherein the pH of the composition is between about
3.2 and about 6.8.
3, A composition in accordance with claim 2 wherein the pH of the composition is between about 3.2 and about 4.8.
3, A composition in accordance with claim 2 wherein the pH of the composition is between about 3.2 and about 4.8.
4. A composition in accordance with claim 1 wherein said buffering, agent comprises acetic acid and sodium acetate.
5. A composition in accordance with claim 1 wherein the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-8-one is between about 50:1 and about 5:1.
6. A composition in accordance with claim 5 wherein the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one is between about 20:1 and about 10:1.
7. A composition in accordance with claim 6 wherein the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one is between about 15:1 and about 13:1.
8. A method of protecting an aqueous-based industrial composition from biological contamination comprising adding an effective amount of a synergistic biocidal composition comprising glutaraldehyde and 1,2-benzisothiazolin-3-one.
9. A method in accordance with claim 8 wherein the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one is between about 17:1 and about 12.5:1.
10. A method in accordance with claim 9 wherein the weight ratio of glutaraldehyde to 1,2-benzisothiazolin-3-one is between about 15:1 and about 13:1.
11. A method in accordance with claim 8 wherein said aqueous-based industrial composition is a calcium carbonate slurry.
12. A method in accordance with claim 8 wherein said aqueous-based industrial composition is a kaolin slurry.
13. A method in accordance with claim 8 wherein said aqueous-based industrial composition is a tape point compound.
14. A method in accordance with claim 8 wherein said aqueous-bused industrial composition is a latex.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US340,935 | 1989-04-20 | ||
| US07/340,935 US5004749A (en) | 1989-04-20 | 1989-04-20 | Concentrated aqueous solution of glutaraldehyde and 1,2-benzisothiazolin-3-one |
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| Publication Number | Publication Date |
|---|---|
| CA2014721A1 CA2014721A1 (en) | 1990-10-20 |
| CA2014721C true CA2014721C (en) | 2000-05-30 |
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ID=23335556
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002014721A Expired - Fee Related CA2014721C (en) | 1989-04-20 | 1990-04-17 | Concentrated aqueous solution of glutaraldehyde and 1,2-benzisothiazolin-3-one |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5004749A (en) |
| EP (1) | EP0393948B1 (en) |
| JP (1) | JP2868839B2 (en) |
| KR (1) | KR0149025B1 (en) |
| AR (1) | AR247804A1 (en) |
| AT (1) | ATE114406T1 (en) |
| AU (1) | AU626658B2 (en) |
| BR (1) | BR9001837A (en) |
| CA (1) | CA2014721C (en) |
| DE (1) | DE69014389T2 (en) |
| DK (1) | DK0393948T3 (en) |
| ES (1) | ES2064622T3 (en) |
| FI (1) | FI103860B (en) |
| IE (1) | IE64985B1 (en) |
| MX (1) | MX163810B (en) |
| NO (1) | NO179852C (en) |
| NZ (1) | NZ233271A (en) |
| PT (1) | PT93803B (en) |
| ZA (1) | ZA902754B (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991007090A1 (en) * | 1989-11-16 | 1991-05-30 | Henkel Kommanditgesellschaft Auf Aktien | Combatting slime-forming microorganisms |
| US5384326A (en) * | 1991-11-12 | 1995-01-24 | Rohm And Haas Company | Girondalones |
| AU5522594A (en) * | 1993-03-03 | 1994-09-08 | W.R. Grace & Co.-Conn. | A method of directly monitoring the concentrations of microbiocides in aqueous systems |
| US5348666A (en) * | 1993-03-31 | 1994-09-20 | Union Carbide Chemicals & Plastics Technology Corporation | Method for stabilizing glutaraldehyde in aqueous systems |
| US5373016A (en) * | 1993-05-28 | 1994-12-13 | Zeneca, Inc. | Protection of isothiazolinone biocides from free radicals |
| ES2152861B1 (en) * | 1998-10-23 | 2001-08-16 | Miret Lab | BIOCIDE-FUNGICIDE COMPOSITION AND PROCEDURE FOR OBTAINING. |
| GB9823247D0 (en) * | 1998-10-24 | 1998-12-16 | Ciba Geigy Ag | A process for the control of microbial contamination in water-based solids suspensions |
| WO2003032730A1 (en) * | 2001-10-16 | 2003-04-24 | Prom Limited | Stable aqueous dispersion of 1,2-benzisothiazoline-3-one (bit) |
| DE102005001566A1 (en) * | 2005-01-13 | 2006-07-27 | Lanxess Deutschland Gmbh | Antimicrobially finished solid preparations |
| KR101562069B1 (en) * | 2006-07-25 | 2015-10-20 | 다우 글로벌 테크놀로지스 엘엘씨 | Stable low voc low viscous biocidal formulations and method of making such formulations |
| US7652048B2 (en) * | 2007-05-04 | 2010-01-26 | Troy Corporation | Water-based, antimicrobially active, dispersion concentrates |
| WO2008148855A1 (en) * | 2007-06-05 | 2008-12-11 | Thor Gmbh | Biocide composition containing glutaraldehyde and at least one isothiazolinone |
| US8497303B2 (en) * | 2008-01-18 | 2013-07-30 | Dow Global Technologies Llc | Method to enhance aqueous solubility of poorly soluble actives |
| US20130150239A1 (en) * | 2010-01-07 | 2013-06-13 | Raman Premachandran | Aqueous-miscible or aqueous-dispersible, voc-free biocidal compositions for the enhanced inhibition of gram-negative bacterial strains, and method of preparing the same |
| JP6040381B2 (en) * | 2013-09-13 | 2016-12-07 | 株式会社片山化学工業研究所 | Method for preventing caking of granulated blast furnace slag and aqueous solution of caking inhibitor used therefor |
| US10743535B2 (en) | 2017-08-18 | 2020-08-18 | H&K Solutions Llc | Insecticide for flight-capable pests |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA784934B (en) * | 1977-09-30 | 1979-10-31 | Ici Ltd | Solutions of benzisothiazolinones |
| DE3144137A1 (en) * | 1981-11-06 | 1983-05-19 | Schülke & Mayr GmbH, 2000 Norderstedt | Surface disinfectants |
| CA1204981A (en) * | 1982-04-19 | 1986-05-27 | Richard P. Clifford | Biocide |
| JPS60234860A (en) * | 1984-05-08 | 1985-11-21 | Hitachi Ltd | Heat transfer printer |
| DE3600271A1 (en) * | 1986-01-08 | 1987-07-09 | Cassella Ag | AQUEOUS PREPARATION OF 1,2-BENZISOTHIAZOLIN-3-ON |
-
1989
- 1989-04-20 US US07/340,935 patent/US5004749A/en not_active Expired - Fee Related
-
1990
- 1990-04-10 NZ NZ233271A patent/NZ233271A/en unknown
- 1990-04-10 ZA ZA902754A patent/ZA902754B/en unknown
- 1990-04-11 AU AU53173/90A patent/AU626658B2/en not_active Ceased
- 1990-04-12 ES ES90304015T patent/ES2064622T3/en not_active Expired - Lifetime
- 1990-04-12 DK DK90304015.2T patent/DK0393948T3/en active
- 1990-04-12 EP EP90304015A patent/EP0393948B1/en not_active Expired - Lifetime
- 1990-04-12 DE DE69014389T patent/DE69014389T2/en not_active Expired - Fee Related
- 1990-04-12 AT AT90304015T patent/ATE114406T1/en not_active IP Right Cessation
- 1990-04-17 CA CA002014721A patent/CA2014721C/en not_active Expired - Fee Related
- 1990-04-18 NO NO901703A patent/NO179852C/en not_active IP Right Cessation
- 1990-04-19 IE IE140290A patent/IE64985B1/en not_active IP Right Cessation
- 1990-04-19 PT PT93803A patent/PT93803B/en not_active IP Right Cessation
- 1990-04-19 MX MX20382A patent/MX163810B/en unknown
- 1990-04-19 BR BR909001837A patent/BR9001837A/en not_active IP Right Cessation
- 1990-04-20 AR AR90316685A patent/AR247804A1/en active
- 1990-04-20 FI FI901988A patent/FI103860B/en not_active IP Right Cessation
- 1990-04-20 KR KR1019900005553A patent/KR0149025B1/en not_active IP Right Cessation
- 1990-04-20 JP JP2105144A patent/JP2868839B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AR247804A1 (en) | 1995-04-28 |
| PT93803B (en) | 1996-09-30 |
| NO901703D0 (en) | 1990-04-18 |
| FI901988A0 (en) | 1990-04-20 |
| US5004749A (en) | 1991-04-02 |
| KR0149025B1 (en) | 1998-08-17 |
| FI103860B1 (en) | 1999-10-15 |
| DK0393948T3 (en) | 1995-01-16 |
| DE69014389D1 (en) | 1995-01-12 |
| FI103860B (en) | 1999-10-15 |
| KR900015612A (en) | 1990-11-10 |
| AU626658B2 (en) | 1992-08-06 |
| DE69014389T2 (en) | 1995-04-20 |
| NO179852B (en) | 1996-09-23 |
| ATE114406T1 (en) | 1994-12-15 |
| JP2868839B2 (en) | 1999-03-10 |
| ZA902754B (en) | 1991-02-27 |
| NO179852C (en) | 1997-01-02 |
| EP0393948A1 (en) | 1990-10-24 |
| IE901402L (en) | 1990-10-20 |
| PT93803A (en) | 1990-11-20 |
| ES2064622T3 (en) | 1995-02-01 |
| NZ233271A (en) | 1991-08-27 |
| IE64985B1 (en) | 1995-09-20 |
| NO901703L (en) | 1990-10-22 |
| EP0393948B1 (en) | 1994-11-30 |
| JPH0363204A (en) | 1991-03-19 |
| BR9001837A (en) | 1991-06-18 |
| AU5317390A (en) | 1990-10-25 |
| CA2014721A1 (en) | 1990-10-20 |
| MX163810B (en) | 1992-06-22 |
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